Homologous recombination repair status in metastatic prostate cancer by next-generation sequencing and functional immunofluorescence.

• Tác giả: Daniel Aguilar, Sara Arce-Gallego, Gisela Mir Arnau, Joan Carles, Irene Casanova-Salas, Sarai Cordoba-Terreros, Pablo Cresta Morgado, Sara Cros, Mercè Cuadras, Matias de Albert, Luisa Delgado-Serrano, Rodrigo Dienstmann, Mariona Figols, Macarena Gonzalez, Alba Llop-Guevara, Xavier Maldonado, David Marmolejo, Alba Mas, Richard Mast, Joaquin Mateo, Rafael Morales-Barrera, Lara Nonell, Paolo Nuciforo, Jacques Planas, Paula Romero-Lozano, Maria Eugenia Semidey, Violeta Serra, Sara Simonetti, Cristina Suarez, Ana Vivancos
• Ngôn ngữ: eng
• Ký hiệu phân loại: 152.1 Sensory perception
• Thông tin xuất bản: United States : Cell reports. Medicine , 2025
• Bộ sưu tập: NCBI
• ID: 679500

Tóm tắt

 Metastatic prostate cancer (mPC) is enriched for homologous recombination repair (HRR) gene alterations, which have prognostic and predictive value. Routine clinical implementation of next-generation sequencing (NGS) is still limited. We investigated the association between genomic and functional loss of HRR, using NGS and RAD51 immunofluorescence (RAD51-IF) in 219 primary or metastatic biopsies from 187 patients with stage IV prostate cancer. NGS showed frequent genomic alterations in TP53 (40%), AR (15%), PTEN (14%), FOXA1 (12%), MYC (10%), BRCA2 (9%), ATM (8%), and BRCA1 (2%). We pursued RAD51-IF in 206 samples
  of those, 139/206 (67%) were evaluable. 21% of samples had RAD51-low score compatible with HRR deficiency (HRD). RAD51-IF showed high sensitivity (71%) and specificity (86%) for BRCA1/2 alterations. Patients with RAD51-low scores experienced longer progression-free survival (PFS) on poly(ADP-ribose) polymerase inhibitors (PARPi) or platinum chemotherapy. RAD51-IF is feasible in routine clinical samples from patients with mPC and is associated with clinically relevant HRR gene alterations.